Medicament vehicles or emulsions



Patented Aug. 7, 1945 MEDICAMENT VEHICLES B EMULSIONS Morton E. Crowe,Tulsa, Okla., assignor to Crows Chemical Company, Tulsa, Okla., acorporation at Oklahoma No ills-swing. Application .lanuary 15, 1945,Eierial No, 572,965

3 @ilaims. 131- 167-58) This invention relates to a medicament vehicle;and has special reference to a liquid vehicle that is, and thatpossesses all of the attributes and characteristics of, a truewaterphase emulsion, and which functions to suspend indefinitely orpermanently different respective medicative substances.

A general object of the invention is to provide a medicament vehicle inthe form of a true waterphase emulsion that remains constant and unvaried in quality for indefinitely long periods of time during varyingtemperatures; that will not deteriorate nor become rancid as a result ofageing, but will remain table and applicable to its intended beneficialmedicative uses when properly packaged and sealed; which may be dilutedwith additional distilled water or normal saline solution when saidadditional dilution is desired, or is needed in order to modify therelative'proportions of the medicaments to the entire prepartion; andwhich will function as a vehicle for the suspension of both soluble andsolid medicaments to be applied and spread topically. The vehicle of thepresent invention, which attains this objective, is and possesses theindispensable characteristics and qualities of a true water-phaseemulsion; is freely dispersible in watery exudates or serous dischargesof the body; is wholly withoutgreasy feel or appearance; is free fromsaponifled fatty acids; is easily applied and easily removed, and doesnot soil clothing; has and shows Brownian movements whenexamined under amicroscope of high power; is capable of wetting either a watery or oilysurface; and has detergent and foaming properties.

- Specific objects of the invention are to provide an improvedwater-phase emulsion for topical application which may be diluted withsterile water or normal saline solution to a desired consistency, and isinhibitory to certain bacteria, for example, Staphylococcus aureus; andto provide an improved emulsion having detergent properties, andisapplicable to the following beneficial uses: For softeningadherentdressings on burns, skin grafts, and other wounds, in order thatsaid dressings may be easily and painlessly removed without interferenceto or with granulation tissue; for debridingwounds and adjacent areaswithout trauma; for use in the treatment of wounds wherevenitdsdmgssibleor diflicult to secure bandages; for saturatihfgauzeato beused asnon-drying drainage packs for post-operative \treatment of nasal,mastoidal. and other surgical wounds; for the treatment of burns even tothe third degree; and for the treatment of certain affections due toallergenic conditions. Due to osmosis or osmotic pressure, a certainamount of this medicament vehicle or true water-phase emulsion isbelieved to penetrate the skin in an unchanged condition, and it hasbeen used with highly satisfactory results in cases which did not reactto the beneficial extent desired to other known treatments.

' Other specific objects of the invention are to provide an improvedwater-phase emulsion functioning as a medicament vehicle for thepermanent suspension of particles of solid medicament's reduced to sucha degree of fineness by proper milling action that said particles remainin suspension permanently, providing a medicated vehicle having theappearance of a smear even when examined through a microscope of highpower such, for instance, as 1000 power. Such a medicated vehicle, doesnot interfere with the therapeutic action of the medicament; does notwall oil? the medicament from the affected area as do many or allsemi-solid grease vehicles, or those containing saponifled fatty acids,waxy products, or gums; is compatible, with most of the medicaments ofthe physicians choice; suspends the medicament uniformly and in easilycontrolled proportions;- facilitates application of the medicament;disperses exudates of tissues and invading organisms without chemical orphysical change; remains where it is applied and protects the affectedarea against further invasion; is non-irritating, non-drying, and ispleasing to the patient; may, be easily removed, if the incorporatedmedicament is irritating, by flushing with sterile water or normalsaline solution; is analgeslc, is readily absorbed by gauze; and aidsthe medicament to peneti'ate into minute dermal crevices. The Brownianmovements, which are prevalent, in and characterize this true water'-phase emulsion, greatly facilitate such desirable penetration andenhance the therapeutic proper ties of the incorporated medicament byconstantly bringing particles of the medicament into contact with theseat of the aflection. Since this' true water-phase emulsion ormedicament vehicle produces and is characterized by Brownian movementsand has great wetting properties, clinical data indicate that lesseramounts of the medicament of choice are required than are now prescribedby the United States and British Pharmacopoeias for ointments. Forexample, 8%

of sulfur suspended in this true water-phase emulsion has been found toproduce results equivalent to at least 20% of sulfur in ointments ofwhich I have knowledge.

, This medicament vehicle or true water-phase emulsion, regardless ofwhether it is for use alone, or for use ,with medicaments suspended,dispersed, or in solution therein, is composed of a mixture or solutionof the following ingredients in about the critical proportions or withinthe critical ranges, by weight, stated: About 0.5% of a constituent ormixture of ingredients functioning as an aromatic and also as ananti-oxidant, dissolved or diluted in 60 o to 65% of the base oil ordispersed phase," consisting of a chemically pure vegetable, animal,mineral, synthesized, or equivalent oil, preferably chemically pureodorless and tasteless castor oil; a water phase consisting of anemulsifying agent composed of a mixture of 1% of superfatted sulfonatedcastor oil, and of 1% to 2% of a sulphate of one of the higher alcoholssuch as lauryl; of 1% to 1.25% of boric acid, 0.9% to 1% of chemicallypure glycerine; and the balance distilled water. when desired orprescribed, an antiseptic may be added in the mixture, such asphenylmercuric borate 1:15,000, or others as prescribed. The mixtureofthe anti-oxidant and persed phase, and the "water phase are thenintermixed and processed, as hereinafter described. These percentagesare critical percentage ratios of the respective constituents to thecompleted vehicle of true water-phase emulsion considered as 100%.

A mixture that functions satisfactorily as an anti-oxidant, as apleasing aromatic, and as a stabilizer to prevent deterioration of thevehicle or water-phase emulsion for long periods of time, is composed ofthe following ingredients in about the proportions by measure stated:

oil constituting the "dis-,

Parts Anisic aldehyde), 10 Benzyl acetate FFC 1. 30 Phenyl ethyl alcohol100 Phenyl acet aldehyde 10 Trpineol 1 Geraniol 300 Hydroxycitronellal50 Muskzylol artificial 10 Alpha anyl cinnamic aldehyde 50 Oilcananga-.. 4 Oil jasmine ar fi 10 Oil neroli artificial 15 Cinnamicalcohol 40 Oil lily valley artificial -1 20 Qulnol 350 Another suchsuitable aromatic anti-oxidant that has been found satisfactory, aspleasingly aromatic, as a stabilizer, and as a preventive ofdeterioration of the vehicle for a long period of time, consists of thefollowing ingredients in about the proportions by measure stated:

appearance of a smear In making this medicament vehicle or true sistingof a mixture of superfatted sulfonated castor oil and a sulphate of oneof the higher alcohols is mixed with the "water phase" consisting ofboric acid, the glycerine, the antiseptic, and the water, in about thecritical proportions by weight above stated. The order in which the saidingredients are mixed to form the said "water phase is unimportant. Thearomatic anti-oxidant is soluble in and is mixed with the base oil ordispersed phase, consisting, preferably, of chemically pure odorless andtasteless castor oil. in about the stated proportions by weight whichare critical. These two separate mixtures comprising the said waterphase" and the said dispersed phase" solutions are then thoroughly andevenly mixed together by mechanical agitation to form a coarse emulsion.Said coarse emulsion is then passed through a colloid mill one or moretimes, and as many times as necessary, to produce a very fine emulsionhaving the without apparent granulation, even when examined through amicroscope of high power, such as a microscope of 1000 power. Thereduction of the oil particles, and all particles, to this degree offineness greatly increases the capability of the emulsion when topicallyapplied alone, or when diluted and topically applied for the treatmentof certain affections and injuries, or when used to incorporate andsuspend subsequently added medicaments for the treatment of affectionsand injuries.

The fine emulsion obtained by proper colloid milling of the coarseemulsion as aforesaid has been used in a great many instances, and maybe used, as a vehicle or emulsion to suspend various prescribed solidmedicaments in a finely comminuted state for the treatment of many skinaffections and wounds. Varying amounts of different prescribed solidmedicaments ranging from 1% to by weight as compared with the weight ofthe vehicle, have been used in the to apply. The

mum that can be suspended in and by the vehicle to any lower amount mostbeneficial for the affections to be treated. The prescribed amount ofsolid medicament to be used in the vehicle for ..the treatment of anaffection is first thoroughly diffused by agitation in the water phase.'By the term water-phase is meant the above described mixture consistingof the emulsifying agent (superfatted sulfonated castor oil and asulphate of one of the higher alcohols), glycerine, antiseptic, andwater, in the proportions by weight stated. Said agitation and diffusioncompletely wets'all exposed surfaces of all particles of said solidmedicament by the emulsifying agent or agents which function as asurface tension depressant on said particles. Next, the said waterphasecontaining the prescribed amount of solid medicament is addedto'andmixed with the other "ingredients, consisting of the aforesaid mixtureof the base oil of dispersed phase, and the aromatic anti-oxidanLin theproportions stated. The mixture of the entii'ETehiclwLwater-phaseemulsion and the prescribed solid medicament is then pa ggdt a ormoretimeathrough a colloid mil'l 'aid is processed thereby to such adegree of fineness that said solid medicament remains D manently insuspension in said vehiclev or emu/ sesame blend-;;,tiiis his.tiiittttii 582156, and" thesmoothly blended mixture of said pasty massand said vehicle or water-phase emulsion is stirred by a mechanicalmixer or otherwise; then the balance of the aforesaid vehicle orwaterphase emulsion to obtain the desired proportions Y in the finishedproduct is added during further mechanical mixing. Thereafter, theentire mixture consisting of the said vehicle or water-phase emulsion,and the pasty mass, is passed through a colloid mill until the solidparticles are reduced to or below the dimensions stated. That is, untilsaid particles are reduced to dimensions such that, when viewed througha 1000 power microscope, they present an appearance of a smooth smearwithout apparent granulation. The methylcellulose functions to reducethe freezing point of'the final product several degrees below freezingpoint of water, which is recognized as 32 F.

Any'prescribed medicament which is not elec-' trolytic or otherwiseincompatible may be suspended or placed in solution in this medicamentvehicle. Medicaments which have been satisfactorily incorporated in thisvehicle include mercurous chloride or calomel, calamine, coppersulphate, sulfur, menthol, beta naphthol; pine tar, penicillin,allantoin, rotenone, dried blood products, phenol, salicyclic acid,tannic acid, ammoniated mercuric chloride, camphor, crysarobin,xeroform, certain tissue growth promoting factors-vitamins, variousantiseptical dyes such as acrofiavin, sulfathiazole, sulfanilamide', andother sulfa compounds, in varying quantities below prescribed maximumamounts alone, or in com bination.

This vehicle or water-phase emulsion has been used for the suspension ofturpentine as a medicament in prescribed amounts, ranging upwardly from1% to or more, by weight, as compared with the weight of the vehicle.The prescribed amount of turpentine to be used as a medicament may bemixed with and diffused in the vehicle to form a new product that isvery penetrating and is non-irritating. Clinical data have indicated thenon-irritating character of this product even when applied by frictionto the area being treated. In numerous instances, the vehicle containingturpentine within the ranges stated has been applied by massaging forthe relief of inflamed or sore muscles, relief of chest colds by counterirritation, and as a lubricant and stimulant in massaging andosteopathic manipulation of the body.

It is an indispensable and unfailing characteristic of the presentinvention that the vehicle or fine emulsion obtained as described is atrue water-phaseemulsion and is substantially free from grease, so thatit is dispersible with water and with watery and oily exudations andscoretions. The greasy ointment bases heretofore genamount: 9 hQE erallyused form envelopes around comminuted ments use ,vm ay skin affectionsand injuries for which the preparation is intended as a treatment.

, This is a continuation, in part, of priorv applications Serial No.343,155, filed June 29, 1940, and Serial No. 415,432, filed September17, 1941. I contemplate the foregoing and such other variations as maybe within the range of equivalents and within the scope oftheappendedclaims.

I claim:

1; A true water-phase fine emulsion free from granulation and havingBrownian movements, comprising by weight to of chemically pure vegetableoil, and about 0.5% of an antioxidant dissolved in said oil; anemulsifying agent composed of amixture of about 1% of superfattedsulfonated castor oil and 1% to 2% by weight of a sulphate of a higheralcohol; from 1% to 1.25% of boric acid, 0.9% to 1% of hemically pureglycerine, and the balance distil ed water.

2. A true water-phase fine emulsion free from granulation and havingBrownian movements'for applying medicaments to skin affections,consistingby weight of 60% to 65% of chemically pure vegetable oilsupporting in solution about-0.5%

. of an anti-oxidant, 1% to 2% of a sulphate of a movements and alsohaving the appearance of a smear without apparent granulation whenexamined with a microscope of high power.

3.. A true water-phase fine emulsion free from granulation and havingBrownian movements for applying medicaments to skin afiections,consisting by weight of 60% to 65% ofchemically pure vegetable 011,about 0.5% of an aromatic antioxidant, about 1% to 2% of a sulphate of ahigher alcohol, about 0.9% to 1% of glycerine, approxiimately 1% ofsulfonated castor oil, about 1% to 1.25% of boric acid, a minim of anantiseptic, and the balance distilled water to make mixed with theproportion, by weight, of 1% to- 30% of turpentine as compared with the100% of said other ingredients.

4. A true water-phase emulsion free from granulation and having Brownianmovements for applying sulfur to skin affections, consisting by weightof about 0.5% of an anti-oxidant, 60%

to 65% of chemically pure odorless and tasteless castor oil, about 1% to2% of a sulphate of a higher alcohol, 0.9% to 1% of glycerine,approximately -1% of a sulfonated castor oil, about 1% to 1.25% of boricacid, and the balance distilled water to make 100%; and sulfur suspendedin said emulsion and applied thereby to the affected area of skinaffection by said Brownian movements.

5. A true water-phase fine emulsion free from granulation and havingBrownian movements. comprising 60% to 65% of chemically pure vegebecases and types of table oil, and. about 0.5% 01' a stable anti-oxidantdissolved in said oil; an emulsifying agent composed of a mixture ofabout 1% of superiatted sulionated castor oil, and 1% to 2% or asulphate 01 a higher cohol; from 1% to 1.25% o! boric acid. from 0.9 oto 1% of chemically pure glycerine, and the balance distilled water, allof said proportions being by weight and forming a complete emulsionhaving a weight of 100%.

6; A true water-phase fine emulsion tree from granulation and havingBrownian movements,

comprising 80% to 65% of chemically pure oil. and about 0.5% or a stableanti-oxidant dissolved in said oil: an emulsifying agent composed 01 amixture of about 1% of superfatted'sultonated castor oil,.and 1% to 2%of a sulphate oi'a higher .alcohol; from l% to 1.25% of borlc acid, from0.9% to 1% of chemically pure glycerine, and the balance distilledwater, all of said. proportions being by weight and forming a complete10 emulsion having a weight 01' 100%.

MORTON B. CROWE.

